Low levels of IgG recognizing the alpha-1-antitrypsin (A1AT)

61 The aim of this study was to examine oxidative stress and low level of alpha62 1-antitrypsin (A1AT) in primary Sjögren's syndrome (pSS), and evaluate the 63 associated autoreactivity against unmodified and their 4-hydroxy-2-nonenal (HNE)64 modified peptides with pSS. Two differentially expressed proteins, alpha-1-acid 65 glycoprotein 1 (A1AG1) and A1AT, exhibited 2-fold differences, and their HNE 66 modifications were identified by depleted-albumin and immunoglobulin G (IgG) 67 serum protein, in-solution digestion, in-gel digestion, and nano-LC-MS/MS from pSS 68 patients and age-matched healthy controls (HCs). Furthermore, levels of proteins, 69 confirmation of HNE modifications, HNE-protein adducts and autoreactivity against 70 unmodified and their HNE-modified peptides were further validated. Levels of the 71 HNE-protein adduct and A1AG1 were significantly higher in pSS patients than HCs, 72 but levels of A1AT were significantly lower in pSS patients compared to HCs. Only 73 the HNE modification of A1AT was confirmed. Further, concentrations of anti74 A1AT50-63 IgG and anti-A1AT50-63 HNE IgA were significantly lower in pSS patients 75 than HCs. Our study suggests that elevated HNE-protein adduct, oxidative stress, 76 level [odds ratio (OR) 4.877, p = 0.003], lowered A1AT level (OR 3.910, p = 0.010) 77 and a decreased level of anti-A1AT50-63 IgG (OR 3.360, p = 0.010) showed an 78 increased risk in pSS patients compared to HCs, respectively. 79 80 Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 30 October 2017 doi:10.20944/preprints201710.0180.v1 Peer-reviewed version available at Int. J. Mol. Sci. 2017, 18, 2750; doi:10.3390/ijms18122750